NEF_TCRZ_PROJECT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 人类免疫缺陷病毒(HIV-1，HIV-2)和猴免疫缺陷病毒(SIV)阴性因子(Nef)是一种在病毒复制周期早期大量表达的27-34 kDa的病毒辅助蛋白。Nef在病毒复制过程中是必不可少的，它在增加HIV感染的致病性和毒力方面发挥了重要作用，部分是通过调节T细胞活性，可能是通过它与T细胞受体(TCRzeta)的Zeta信号链的相互作用。目前，我们已经结晶了包含SIV Nef核心区和TCRzeta片段的络合物，并在我们自己的来源获得了高达6-8A的衍射数据。获得更强大的光束线将产生更高分辨率的数据，这应该允许确定复合体的高分辨率结构。Nef-TCRzeta复合体的结构细节不仅揭示了每个蛋白质上的相互作用部位，而且还提供了Nef如何通过TCR诱导免疫调节活性的洞察。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human immunodeficiency virus (HIV-1, HIV-2) and simian immunodeficiency virus (SIV) negative factor (Nef) is a 27-34 kDa viral accessory protein expressed in abundance early in the viral replicative cycle. Dispensable during viral replication, Nef plays an important role in increasing the pathogenicity and virulence of an HIV infection in part by modulation of T-cell activity, presumably through its demonstrated interaction with the zeta signaling chain of the T-cell receptor (TCRzeta). At present, we have crystallized a complex containing the core domain of SIV Nef and a fragment of the TCRzeta and obtained diffraction data up to 6-8A at our home source. Access to a more powerful beamline will result in higher resolution data that should allow for determination of a high resolution structure of the complex. Structural details of the Nef-TCRzeta complex will reveal not only the interaction sites on each protein but also provide insight into how Nef induces immunomodulatory activity through the TCR.